Summary: Research in the Interventional Radiology (IR) lab is motivated by the fact that image guidance and minimally invasive approaches have revolutionized the management of many common diseases. However, diagnosis and therapy remain distinctly separated from each other in both time and space. We believe that this gap between diagnosis and therapy can be narrowed by minimally invasive image guided therapies and with the application of novel guidance technologies and engineered vectors. All research efforts in the IR lab are developed with a clear translational route to the clinic and address areas of urgent clinical need. The IR labs research program is separated into three main areas: electromagnetic (EM) and optical tracking and robotics, drug + device combinations, novel methods of augmentation of ablative energies (RFA, MWA, Laser, IRE, or HIFU). The diversity of these projects requires an interdisciplinary team of researchers and takes full advantage of the interdisciplinary resources found within the Clinical Center and the Intramural Research Program of the National Institutes of Health. We believe that combining the imaging tools inherent to interventional radiology with pharmaceuticals and medical devices can make a significant contribution to the future treatment of both localized and systemic diseases, with an emphasis upon cancer therapeutics. Principal projects are: 1) Smart biopsy, 2) OR of the future and, 3) Drugs + devices. Smart biopsy relies upon precise electromagnetic tracking to target tissue to correlate sample with imaging parameters. OR of the future is a broad translational project that integrates a variety of technologies for navigation, automation, and visualization of medical procedures. Sub-projects within the Drug + Device model include: 1) Temperature sensitive liposomes combined with radiofrequency ablation (RFA) or high intensity focused ultrasound (HIFU), 2) Radiofrequency ablation combined with immunotherapy / checkpoint inhibitor therapy, and 3) Development of image-able drug eluting beads (DEB) for transcatheter arterial chemoembolization (TACE). The clinical treatment of solid tumors could be improved by controlling the pharmacologic properties of anticancer therapeutics to deliver a greater dose to the tumor; with conventional drugs, this dose is typically limited by toxic side effects in normal tissues. Therefore, the efficacy of current anticancer treatments may be improved with advances in drug delivery technologies that have received increased attention in recent years. The goal of drug delivery in the treatment of cancer is to increase the concentration of a therapeutic agent in the tumor while limiting systemic exposure and subsequent normal tissue toxicity. The combination of drug delivery technologies with image guided interventions represents a rich field with great translational potential and the ability to bridge the gap between diagnosis and therapy. Diagnosis and therapy remain distinctly separated from each other in time and space. The gap between diagnosis and therapy can be closed by minimally invasive image guided therapies. Real-time, intra-procedural tools will blend diagnosis and therapy into a dynamic, iterative process with improved outcomes. The redefining of surgical-like procedures will be fueled by multi-modality imaging, navigation, visualization, robotics, and automated precision tools. These enabling technologies have not yet been optimally applied to existing clinical problems, especially in minimally-invasive image guided therapies. This presents an opportunity to integrate these technologies into the clinical setting in a validated and cost-effective manner, and to study the impact prior to broad implementation. Image guidance and multimodality navigation will fuel a small revolution in procedural medicine, which presents unprecedented opportunity and challenge. Image guidance and minimally invasive approaches have revolutioniiized themanagement of many common diseases. The miniaturization of surgical interventions has seen the broad adoption of needle or catheter-based procedures such as tumor embolization, brain aneurysm coiling, aortic stent grafting, uterine fibroid embolization, atherosclerosis stenting and angioplasty, and tumor thermal ablation with radiofrequency. As procedures are becoming less and less invasive, they are more and more targeted and guided by imaging and spatial information. The ability to navigate a medical device to a target based upon multiple windows or multiple modalities should have tremendous advantages in certain settings. The combination of functional and morphologic (metabolic and anatomic) information on the same coordinate system is empowering. With multiple public and private partners, we have developed a multimodality interventional radiology suite that uses a CT coordinate frame to co-register and co-localize different devices including pre-procedural images, intra-procedural ultrasound, CT, rotational fluoroscopy, robotics, electromagnetic tracking and therapeutic ultrasound, microwave, radiofrequency, etc. to allow the best combinations of techniques and guidance methods tailored to the particular patients needs. Combining imaging modalities can take advantage of each modality's strength. Real-time feedback and temporal resolution of ultrasound can be combined with the functional and metabolic data from PET and the spatial resolution of MR or CT, all on one seamless platform for treatment planning, targeting, procedural navigation, monitoring, and verification of treatment.The lab has continued the electromagnetic tracking clinical trial with over 2000 patients. The lab also further studied Medical GPS for tumor ablation and treatment planning and for prostate biopsies using MRI information without requiring an MRI to be physically present. We have also started work in preparation for using other vendor's ultrasound source images for fusing real time ultrasound with pre-op images (CT, MRI, PET, etc). This study yielded numerous discoveries, papers, and commercialized products. Also as a result of this work, numerous vendors in the field have adopted similar multi-modality approaches. Phase I of laser ablation of prostate cancer under MRI guidance was completed and Phase II submission is in process for using ultrasound alone to guide the prostate cancer ablation. Low tech, low cost methods for navigation continued, including laser guidance for needle based biopsy and ablation, and bronchoscopy navigation and laser ablation development. Preclinical work is in process for focal prostate therapies (laser ablation with real-time MRI fluoroscopy) and clinical studies to plan and deliver a composite ablation treatment. A clinical trial is underway to study angle selection techniques and assess accuracy of CT integrated robot-like devices. Drug eluting beads as a tool for regional therapies was refined in preclinical models and will be combined with image-able beads that show where the drug is being delivered in liver chemoembolization with drug dluting beads. Image-able drug eluting beads are being studied and refined in preclinical models and clinic, in order to develop drug dose planning software. Conductive catheters and endovascular devices and embolization devices were studied and prototyped, and NIH patents were issued on devices. Optical needle endoscopy was prototyped and will be tested in CC patients next FY.